Free and complexed-secretory immunoglobulin A triggers distinct intestinal epithelial cell responses.

Secretory immunoglobulin A (SIgA) antibodies play an important role in protecting the mucosal surfaces against pathogens and maintaining homeostasis with the commensal microbiota. Because a substantial portion of the gut microbiota is coated with SIgA, we hypothesized that microbiota-SIgA complexes are important for the maintenance of gut homeostasis. Here we investigated the relationship between microbiota-SIgA complexes and inflammatory epithelial cell responses. We used a multi-cellular three-dimensional (3D) organotypical model of the human intestinal mucosa composed of an intestinal epithelial cell line and primary human lymphocytes/monocytes, endothelial cells and fibroblasts. We also used human SIgA from human colostrum, and a prominent bacterial member of the first colonizers, Escherichia coli, as a surrogate commensal. We found that free and microbiota-complexed SIgA triggered different epithelial responses. While free SIgA up-regulated mucus production, expression of polymeric immunoglobulin receptor (pIgR) and secretion of interleukin-8 and tumoir necrosis factor-α, microbiota-complexed SIgA mitigated these responses. These results suggest that free and complexed SIgA have different functions as immunoregulatory agents in the gut and that an imbalance between the two may affect gut homeostasis.

Tourettism in multiple sclerosis: a case report.

The term Tourettism refers to Tourette Syndrome (TS)-like symptoms which appear secondary to a variety of both acquired and congenital neurological and neuropsychiatric disorders or following an exposure to several drugs. The association between Tourettism and Multiple Sclerosis (MS) is very rare. Only two cases of patients affected by MS who also showed a simple phonic tic and complex vocal tics respectively have been reported. The case here described reports of a 30 year-old woman affected by secondary-progressive MS who developed, 7 years after the onset of the disease, TS-like symptoms which were responsive to quetiapine. At that time her brain MRI, when compared with the previous scan, showed an increased lesion burden and an increased atrophy in the regions around Sylvian fissures. Considering recent findings on TS, the increased atrophy in these strategic brain regions could be responsible for the tics onset in our patient. At the same time, the diffuse involvement of the white matter and the progressive brain atrophy which we observed could have impaired the cortico-striato-thalamo-cortical circuits consistently implicated in the pathogenesis of TS. In conclusion, we can hypothesize that in our case Tourettism and MS could be considered causal related more than coincidentally associated.

Bromelain prevents secretion caused by Vibrio cholerae and Escherichia coli enterotoxins in rabbit ileum in vitro.

BACKGROUND & AIMS: Diarrhea is a major cause of illness and death in children and young animals. The aim of this study was to investigate the possible therapeutic effect of bromelain, a proteolytic extract obtained from pineapple stems on bacterial toxin and second-messenger agonist-induced intestinal secretion. METHODS: The effect of bromelain pretreatment on short-circuit responses to Escherichia coli heat-labile enterotoxin, heat-stable enterotoxin, and Vibrio cholerae cholera toxin was evaluated in rabbit ileum mounted in Ussing chambers. RESULTS: Bromelain was 62% effective in preventing heat-labile enterotoxin-induced secretion, 51% effective against cholera toxin, and 35% effective against heat-stable enterotoxin [corrected]. Bromelain also prevented secretory changes caused by prostaglandin E2, theophylline, calcium-ionophore A23187, 8-bromoadenosine 3':5'-cyclic monophosphate, and 8-bromoguanosine 3':5'-cyclic monophosphate, well-known intracellular mediators of ion secretion. The efficacy of bromelain was not caused by reduced tissue viability resulting from its proteolytic effects on enterocytes, indicated by experiments measuring uptakes of nutrients into intestinal cells and experiments measuring short-circuit responses to glucose. CONCLUSIONS: Bromelain prevents intestinal fluid secretion mediated by secretagogues that act via adenosine 3':5'-cyclic monophosphate, guanosine 3':5'-cyclic monophosphate, and calcium-dependent signaling cascades. It may be clinically useful as an antidiarrheal drug.

Diarrhoea in jaundiced neonates treated with phototherapy: role of intestinal secretion.

Thirty jaundiced neonates with diarrhoea who were being treated with phototherapy and 30 matched control infants were studied to try and find out the cause of the diarrhoea. Faecal osmolality and electrolyte concentrations were measured, which gave clear evidence that the diarrhoea arose from intestinal secretion. Rectal water and electrolyte absorption in 10 jaundiced infants receiving phototherapy, in 10 jaundiced infants not receiving phototherapy, and in 10 healthy controls was measured with a rectal dialysis bag. A further group of eight jaundiced infants was also studied both during and after phototherapy to document the reversal of ion transport changes. Absorption of water, sodium chloride, and potassium was significantly impaired in the patients receiving phototherapy compared with each of the control groups. Such impairment was transient, as it was not apparent when the jaundice faded and phototherapy was stopped. These data show that the colon plays a part in the pathogenesis of secretory diarrhoea and that both hyperbilirubinaemia and phototherapy are necessary for such an effect to develop.

Unconjugated bilirubin and the bile from light exposed Gunn rats inhibit intestinal water and electrolyte absorption.

Jaundiced babies undergoing phototherapy often develop diarrhoea. The cause of it is still uncertain. Increasing evidence supports a role of a secretory mechanism for the diarrhoea. We therefore studied the effects of bile from congenitally jaundiced rats undergoing phototherapy and of unconjugated bilirubin on rat small intestine in vivo and in vitro. Results suggest that: (1) the bile from homozygous Gunn rats under phototherapy has an anti-absorptive effect when tested in the perfused jejunum of normal Wistar rats; (2) unconjugated bilirubin has a dose dependent secretory effect on the intestinal transport of water and electrolytes, when tested in the same system. Alteration of cyclic AMP or cyclic GMP, known intracellular mediators of secretion, was not observed. We conclude that free bilirubin is an intestinal secretagogue acting by an as yet unknown mechanism, that may mediate the secretory type of diarrhoea in jaundiced neonates undergoing phototherapy.